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Why fat angers the immune system

By Deborah MacKenzie

Overweight people get heart disease and diabetes – and more severe swine flu – because their fat triggers inflammation, an immune response meant to fight infection. Now the protein responsible for this sequence of events may have been found.

Jerrold Olefsky and colleagues at the University of California, San Diego, killed the bone marrow cells in mice that make immune cells called macrophages. Then they injected the mice with macrophages lacking a surface protein called TLR4.

When the team fed the mice high-fat diet, all grew obese, as did a group of normal mice. But unlike the normal mice, those with altered macrophages showed no signs of inflammation, such as changes in insulin production, high levels of immune chemicals, and macrophages in their belly fat.

Olefsky concludes that TLR4 mediates the immune system’s response to fat. He says that some fatty acids look like the bacterial invaders that TLR4 senses, prompting normal macrophages to mistake fatty acids for the enemy and turn on inflammation. His team is now testing drugs that block TLR4. One day these might help people dodge some of the health effects of being overweight.